期刊
CELL STEM CELL
卷 8, 期 4, 页码 412-425出版社
CELL PRESS
DOI: 10.1016/j.stem.2011.02.005
关键词
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资金
- Fondation contre la Leucemie
- ARC [3710]
- Inserm
- CEA/DSV
Crosstalk between transcription factors and cytokines precisely regulates tissue homeostasis. Transcriptional intermediary factor 1 gamma (TIF1 gamma) regulates vertebrate hematopoietic development, can control transcription elongation, and is a component of the TGF-beta signaling pathway. Here we show that deletion of TIF1 gamma in adult hematopoiesis is compatible with life and long-term maintenance of essential blood cell lineages. However, loss of TIF1 gamma results in deficient long-term hematopoietic stem cell (LTHSC) transplantation activity, deficient short-term HSC (ST-HSC) bone marrow retention, and priming ST-HSCs to myelomonocytic lineage. These defects are hematopoietic cell-autonomous, and priming of TIF1 gamma-deficient ST-HSCs can be partially rescued by wild-type hematopoietic cells. TIF1 gamma can form complexes with TAL1 or PU.1 two essential DNA-binding proteins in hematopoiesis occupy specific subsets of their DNA binding sites in vivo, and repress their transcriptional activity. These results suggest a regulation of adult hematopoiesis through TIF1 gamma-mediated transcriptional repression of TAL1 and PU.1 target genes.
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